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Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.
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Sistema de Sinalização das MAP Quinases , Osteonectina , Animais , Camundongos , Divisão Celular Assimétrica , Diferenciação Celular , Osteonectina/genética , Transdução de SinaisRESUMO
Splash, one of the most visually apparent droplet dynamics, can manifest on any surface above a certain impact velocity, regardless of surface wettability. Previous studies demonstrate that elevating the substrate temperature can suppress droplet splash, which is unfavorable for many practical applications, such as spray cooling and combustion. Here, we report that the suppression effect of substrate temperature on splash is nullified by utilizing surfaces with nanostructures. By manipulating air evacuation time through surface nanostructures, we have identified a pathway for precise control over the splash threshold and the ability to tailor the dependence of the splash onset on surface temperature. We further propose a theoretical criterion to determine different splash regimes by considering the competition between air evacuation and the development of flow instabilities. Our findings underscore the crucial role of nanostructures in splash dynamics, offering valuable insights for the control of splash in various industrial scenarios.
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Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutation display poor prognosis, and targeted therapy is not available currently. Our previous study identified increased expression of Exportin1 (XPO1) in DNMT3AR882H AML patients. Therefore, we further investigated the therapeutic effect of XPO1 inhibition on DNMT3AR882H AML. Three types of DNMT3AR882H AML cell lines were generated, and XPO1 was significantly upregulated in all DNMT3AR882H cells compared with the wild-type (WT) cells. The XPO1 inhibitor selinexor displayed higher potential in the inhibition of proliferation, promotion of apoptosis, and blockage of the cell cycle in DNMT3AR882H cells than WT cells. Selinexor also significantly inhibited the proliferation of subcutaneous tumors in DNMT3AR882H AML model mice. Primary cells with DNMT3A mutations were more sensitive to selinexor in chemotherapy-naive AML patients. RNA sequencing of selinexor treated AML cells revealed that the majority of metabolic pathways were downregulated after selinexor treatment, with the most significant change in the glutathione metabolic pathway. Glutathione inhibitor L-Buthionine-(S, R)-sulfoximine (BSO) significantly enhanced the apoptosis-inducing effect of selinexor in DNMT3AWT/DNMT3AR882H AML cells. In conclusion, our work reveals that selinexor displays anti-leukemia efficacy against DNMT3AR882H AML via downregulating glutathione pathway. Combination of selinexor and BSO provides novel therapeutic strategy for AML treatment.
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DNA (Citosina-5-)-Metiltransferases , DNA Metiltransferase 3A , Proteína Exportina 1 , Glutationa , Hidrazinas , Carioferinas , Leucemia Mieloide Aguda , Mutação , Receptores Citoplasmáticos e Nucleares , Triazóis , Humanos , Animais , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Carioferinas/antagonistas & inibidores , Carioferinas/genética , Camundongos , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/genética , Glutationa/metabolismo , Hidrazinas/farmacologia , Hidrazinas/uso terapêutico , Triazóis/farmacologia , Triazóis/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação para Baixo/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Masculino , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Type I interferons (IFNs) are an essential class of cytokines with antitumor, antiviral and immunoregulatory effects. However, over-productive the type I IFNs are tightly associated with autoimmune disorders. Thus, the induction of type I interferons is precisely regulated to maintain immune hemostasis. This study aimed to identify a novel regulator of type I interferon signaling. METHODS AND RESULTS: Primary BMDMs, isolated from mice, and human cell lines (HEK293 cells, Hela cells) and murine cell line (MEF cells) were cultured to generate in vitro models. After knockdown VRK1, real-time PCR and dual-luciferase reporter assay were performed to determine the expression level of the type I IFNs and ISGs following HTDNA and Poly (dA:dT) stimulation. Additionally, cells were treated with the VRK1 inhibitor, and the impact of VRK1 inhibition was detected. Upon HTDNA and Poly (dA:dT) stimulation, knockdown of VRK1 attenuated the induction of the type I IFNs and ISGs. Consistently, VRK-IN-1, a potent and selective VRK1 inhibitor, significantly suppressed the induction of the type I IFNs and ISGs in human and murine cell lines. Further, VRK-IN-1 inhibited induction of the type I IFNs in mouse primary BMDMs. Intriguingly, VRK1 potentiated the cGAS-STING- IFN-I axis response at STING level. CONCLUSIONS: Our study reveals a novel function of VRK1 in regulating the production of type I IFNs. VRK-IN-1 might be a potential lead compound for suppressing aberrant type I IFNs in autoimmune disorders.
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Doenças Autoimunes , Interferon Tipo I , Proteínas Serina-Treonina Quinases , Animais , Humanos , Camundongos , DNA/metabolismo , Células HEK293 , Células HeLa , Interferon Tipo I/metabolismo , Interferons , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.
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BACKGROUND: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. METHODS: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5⯵m PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. RESULTS: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-ß/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. CONCLUSION: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-ß1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.
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Focused microwave breast hyperthermia (FMBH) employs a phased antenna array to perform beamforming that can focus microwave energy at targeted breast tumors. Selective heating of the tumor endows the hyperthermia treatment with high accuracy and low side effects. The effect of FMBH is highly dependent on the applied phased antenna array. This work investigates the effect of polarizations of antenna elements on the microwave-focusing results by simulations. We explore two kinds of antenna arrays with the same number of elements using different digital realistic human breast phantoms. The first array has all the elements' polarization in the vertical plane of the breast, while the second array has half of the elements' polarization in the vertical plane and the other half in the transverse plane, i.e., cross polarization. In total, 96 sets of different simulations are performed, and the results show that the second array leads to a better focusing effect in dense breasts than the first array. This work is very meaningful for the potential improvement of the antenna array for FMBH, which is of great significance for the future clinical applications of FMBH. The antenna array with cross polarization can also be applied in microwave imaging and sensing for biomedical applications.
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Neoplasias da Mama , Hipertermia Induzida , Micro-Ondas , Imagens de Fantasmas , Humanos , Micro-Ondas/uso terapêutico , Neoplasias da Mama/terapia , Hipertermia Induzida/métodos , Feminino , Mama/patologia , Simulação por ComputadorRESUMO
INTRODUCTION: Anterior cruciate ligament (ACL) tibial avulsion fracture is a rare injury, which usually happens in adults with traffic accidents or sports injuries. Surgery interventions are common treatment methods, they can restore knee function and help to return to normal life. In this study, we described an arthroscopic modified suture bridge fixation technique for ACL tibial avulsion fractures and explored the feasibility and therapeutic effects. MATERIALS AND METHODS: This retrospective study reviewed data from January 2020 to May 2022. Data were collected on 18 patients (10 males and 8 females) with ACL tibial avulsion fractures and underwent arthroscopic modified suture bridge fixation technique. The study analyzed surgical data about intraoperative blood loss, operation time, hospital stay, fracture healing time, and visual analog scale (VAS). Functional evaluation of the knee joint was performed using the anterior drawer test, Lysholm knee scoring scale, International Knee Documentation Committee (IKDC), and knee range of motion (ROM). RESULTS: All 18 patients were followed up between 12 and 20 months, with an average of 15.22 ± 1.96 months. The intraoperative blood loss was approximately 15-40 mL, averaging 25.78 ± 6.19 mL. The operation time was 65-85 min, with a mean of 74.89 ± 4.86 min. The hospital stay of patients was 3-5 days, with a mean of 3.89 ± 0.76 days. The mean fracture healing time was 8-12 weeks after surgery, with a mean of 9.22 ± 1.7 weeks. All incisions healed grade I without infection. There were no internal fixation failures, neurovascular injuries, and lower extremity deep venous thrombosis. The anterior drawer test was negative in all patients. At the final follow-up, the mean VAS score was 0-3, averaging 1.56 ± 0.71. The Lysholm score of the injured knee was 89-96, with an average of 92.50 ± 2.50; the IKDC score was 88-93, with an average of 90.44 ± 1.89; the knee ROM was 110-126°, with an average of 120.67° ± 4.31°. CONCLUSION: Results demonstrated that the modified suture bridge fixation technique under arthroscope could provide reliable fixation and favorable clinical effects for ACL tibial avulsion fractures. This is a simple, minimally invasive, effective, and clinically applicable surgical method for ACL tibial avulsion fracture.
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Lesões do Ligamento Cruzado Anterior , Artroscopia , Fratura Avulsão , Técnicas de Sutura , Fraturas da Tíbia , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Artroscopia/métodos , Fraturas da Tíbia/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Fratura Avulsão/cirurgia , Adulto Jovem , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentaçãoRESUMO
BACKGROUND: Pan-cancer analysis examines both the commonalities and heterogeneity among genomic and cellular alterations across numerous types of tumors. Pan-cancer analysis of gene expression, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune microenvironment (TIME), and methylation becomes available based on the multi-omics data from The Cancer Genome Atlas Program (TCGA). Some online tools provide analysis of gene and protein expression, mutation, methylation, and survival for TCGA data. However, these online tools were either Uni-functional or were not able to perform analysis of user-defined functions. Therefore, we created the TCGAplot R package to facilitate perform pan-cancer analysis and visualization of the built-in multi-omic TCGA data. RESULTS: TCGAplot provides several functions to perform pan-cancer paired/unpaired differential gene expression analysis, pan-cancer correlation analysis between gene expression and TMB, MSI, TIME, and promoter methylation. Functions for visualization include paired/unpaired boxplot, survival plot, ROC curve, heatmap, scatter, radar chart, and forest plot. Moreover, gene set based pan-cancer and tumor specific analyses were also available. Finally, all these built-in multi-omic data could be extracted for implementation for user-defined functions, making the pan-cancer analysis much more convenient.\ CONCLUSIONS: We developed an R-package for integrative pan-cancer analysis and visualization of TCGA multi-omics data. The source code and pre-built package are available at GitHub ( https://github.com/tjhwangxiong/TCGAplot ).
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Multiômica , Neoplasias , Humanos , Genômica , Instabilidade de Microssatélites , Mutação , Neoplasias/genética , Microambiente TumoralRESUMO
OBJECTIVE: To observe the clinical effect of combined application of Compound Amino Acid Capsule (8-11) (CAAC8-11) and L-carnitine (LC) in the treatment of idiopathic asthenospermia (IAS), and to explore its possible therapeutic mechanism. METHODS: Based on the principle of double-blind and control, we selected 120 cases of IAS meeting the diagnostic criteria of asthenospermia in the WHO Manual for the Examination and Processing of Human Semen (5th Ed) and randomly divided them into three groups of an equal number: CAAC8-11 + LC, LC control and blank control, the former given CAAC8-11 in addition to LC oral liquid, and the latter two given LC oral liquid and life intervention, respectively, all for 12 weeks. We collected semen samples from all the patients before and after treatment, and examined perm motility, the contents of neutral α- glucosidase (NAG) and reactive oxygen species (ROS), sperm DNA fragmentation index (DFI), and the expression of the Nrf2 protein. RESULTS: Compared with the baseline, the total sperm motility was significantly improved in the IAS patients after treated with CAAC8-11 + LC (ï¼»27.50 ± 0.77ï¼½% vs ï¼»32.50 ± 0.74ï¼½%, P < 0.05) or LC only (ï¼»27.60 ± 0.66ï¼½% vs ï¼»30.90 ± 0.70ï¼½%, P < 0.05), dramatically higher in the CAAC8-11 + LC than in the LC and blank control groups (P < 0.01). The content of NAG in the epididymis was remarkably increased after treatment in the CAAC8-11 + LC than in the LC and blank control groups (ï¼»23.90 ± 0.56ï¼½ vs ï¼»21.20 ± 0.49ï¼½ and ï¼»16.80 ± 0.42ï¼½ mU, P < 0.05), so was the expression of Nrf2 (P < 0.05), while the ROS level was markedly decreased in the former than in the latter two groups (ï¼»81.60 ± 2.50ï¼½ vs ï¼»88.50 ± 2.50ï¼½ and ï¼»88.70 ± 2.40ï¼½ µg/ml, P < 0.05). CONCLUSION: CAAC8-11 + LC has a good clinical effect on asthenospermia, with no adverse reactions, which may be attributed to its ability to regulate the high expression of Nrf2, decrease the production of ROS and reduce the damage of oxidative stress to sperm motility.
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Astenozoospermia , Carnitina , Humanos , Masculino , Carnitina/uso terapêutico , Carnitina/farmacologia , Aminoácidos/uso terapêutico , Contagem de Espermatozoides , Sêmen , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Motilidade dos Espermatozoides , Espermatozoides , Astenozoospermia/tratamento farmacológico , alfa-GlucosidasesRESUMO
Microbubble's mass transfer under external acoustic excitation holds immense potential across various technological fields. However, the current state of acoustic technology faces limitations due to inadequate control over bubble size in liquids under external excitation. Here, we conducted numerical investigations of the mass transfer behavior of microbubbles in liquids under multifrequency acoustic excitations with different frequencies (in the MHz range), pressure amplitudes (in the range of several atmospheric pressures), and amplitude ratios. We identified various pressure threshold regions for the growth of gas bubbles (radii range from a few microns to tens of microns) and observed common intersections between single and multifrequency excitations that enable effective control of the growth intervals and final size of bubbles by adjusting the ratio of pressure amplitude and frequency value. Allocating power to the lower frequency component of multifrequency acoustic excitation is recommended to facilitate mass transfer or diffusion, as small-frequency acoustic excitation has a more significant effect than the higher frequency in the growth region. Our study provides a better understanding of the dynamics of bubbles under complex excitations and has practical implications for developing methods to control and promote bubble-related processes.
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PURPOSE: Pancreatic cancer (PACA) is one of the most fatal malignancies worldwide. Immunotherapy is largely ineffective in patients with PACA. T-cell exhaustion contributes to immunotherapy resistance. We investigated the prognostic potential of T-cell exhaustion-related genes (TEXGs). METHODS: A single-cell RNA (scRNA) sequencing dataset from Tumor Immune Single-Cell Hub (TISCH) and bulk sequencing datasets from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to screen differentially expressed TEXGs. Kaplan-Meier survival, LASSO regression, and univariate/multivariate Cox regression analyses were performed to construct a TEXG risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. The PACA cohorts from the ICGC and GSE71729 datasets were used to validate the risk model. Pan-cancer expression of SPOCK2 was determined using the TISCH database. RESULTS: A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Patients with low risk had prolonged survival times in both the training (TCGA-PAAD, n = 178) and validation (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n = 412) datasets. Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PACA. High-risk patients correlated with their immunosuppressive status. Immunohistochemical staining confirmed the changes in TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 may be a novel marker of exhausted CD8+ T-cells. CONCLUSION: We established and validated a T-cell exhaustion-related prognostic signature for patients with PACA. Moreover, our study suggests that SPOCK2 is a novel marker of exhausted CD8+ T cells.
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Objective: Curcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. Method: Using tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. Result: We identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below -1.85 kJ mol-1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. Conclusion: Through in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.
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OBJECTIVE: Metabolic reprogramming serves as a distinctive feature of cancer, impacting proliferation and metastasis, with aberrant glycosphingolipid expression playing a crucial role in malignancy. Nevertheless, limited research has investigated the connection between glycosphingolipid metabolism and pancreatic cancer. METHODS: This study utilized a single-cell sequencing dataset to analyze the cell composition in pancreatic cancer tissues and quantified single-cell metabolism using a newly developed computational pipeline called scMetabolism. A gene signature developed from the differential expressed genes (DEGs), related to epithelial cell glycosphingolipid metabolism, was established to forecast patient survival, immune response, mutation status, and reaction to chemotherapy with pancreatic adenocarcinoma (PAAD). RESULTS: The single-cell sequencing analysis revealed a significant increase in epithelial cell proportions in PAAD, with high glycosphingolipid metabolism occurring in the cancerous tissue. A six-gene signature prognostic model based on abnormal epithelial glycosphingolipid metabolism was created and confirmed using publicly available databases. Patients with PAAD were divided into high- and low-risk categories according to the median risk score, with those in the high-risk group demonstrating a more unfavorable survival outcome in all three cohorts, with higher rates of gene mutations (e.g., KRAS, CDKN2A), increased levels of immunosuppressive cells (macrophages, Th2 cells, regulatory T cells), and heightened sensitivity to Acetalax and Selumetinlb. CONCLUSIONS: Abnormal metabolism of glycosphingolipids in epithelial cells may promote the development of PAAD. A model utilizing a gene signature associated with epithelial glycosphingolipids metabolism has been established, serving as a valuable indicator for the prognostic stratification of patients with PAAD.
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Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers.
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Neoplasias da Mama , Neoplasias Renais , Metiltransferases , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Mama/diagnóstico , Neoplasias Renais/diagnóstico , Metiltransferases/genética , Metiltransferases/metabolismo , Prognóstico , Neoplasias da Próstata/diagnósticoRESUMO
FLOWERING LOCUS T (FT), belonging to the FT/TFL1 gene family, is an important gene regulating the flowering transition and inflorescence architecture during plant development. Given its importance to plant adaptation and crop improvement, FT has been extensively studied in related plant research; however, the specific role and underlying molecular mechanisms of FT in the continuous flowering of perennial plants remains elusive. Here, we isolated and characterized homologous FT genes from two Camellia species with different flowering-period phenotypes: CaFT was isolated from Camellia azalea, a precious species blooming in summer and flowering throughout the year, and CjFT was isolated from C. japonica, which blooms in winter and spring. The major difference in the genes between the two species was an additional five-amino acid repeat sequence in C. japonica. FT showed high expression levels in the leaves in both species from January to August, especially in April for C. japonica and in May for C. azalea. CaFT was expressed throughout the year in C. azalea, whereas CjFT was not expressed from September to December in C. japonica. The expression levels of FT in the floral buds were generally higher than those in the leaves. Overexpression of CaFT and CjFT in Arabidopsis indicated that both genes can activate downstream genes to promote flowering. Transgenic callus tissue was obtained by introducing the two genes into C. azalea through Agrobacterium-mediated transformation. Transcriptome and quantitative real-time polymerase chain reaction analyses indicated that both florigen FT genes promoted the expression of downstream genes such as AP1, FUL, and SEP3, and slightly up-regulated the expression of upstream genes such as CO and GI. The above results indicated that CaFT and CjFT played a role in promoting flowering in both camellia species. The expression pattern of CaFT in leaves suggested that, compared to CjFT, CaFT may be related to the annual flowering of C. azalea.
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Because of its peculiar flavor, chili oil is widely used in all kinds of food and is welcomed by people. Chili pepper is an important raw material affecting its quality, and commercial chili oil needs to meet various production needs, so it needs to be made with different chili peppers. However, the current compounding method mainly relies on the experience of professionals and lacks the basis of objective numerical analysis. In this study, the chroma and capsaicinoids of different chili oils were analyzed, and then the volatile components were determined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-ion migration spectrometer (GC-IMS) and electronic nose (E-nose). The results showed that Zidantou chili oil had the highest L*, b*, and color intensity (ΔE) (52.76 ± 0.52, 88.72 ± 0.89, and 118.84 ± 1.14), but the color was tended to be greenyellow. Xinyidai chili oil had the highest a* (65.04 ± 0.2). But its b* and L* were relatively low (76.17 ± 0.29 and 45.41 ± 0.16), and the oil was dark red. For capsaicinoids, Xiaomila chili oil had the highest content of capsaicinoids was 2.68 ± 0.07 g/kg, Tianjiao chili oil had the lowest content of capsaicinoids was 0.0044 ± 0.0044 g/kg. Besides, 96 and 54 volatile flavor substances were identified by GC-MS and GC-IMS respectively. And the main volatile flavor substances of chili oil were aldehydes, alcohols, ketones, and esters. A total of 11 key flavor compounds were screened by the relative odor activity value (ROAV). Moguijiao chili oil and Zidantou chili oil had a prominent grass aroma because of hexanal, while Shizhuhong chili oil, Denglongjiao chili oil, Erjingtiao chili oil, and Zhoujiao chili oil had a prominent floral aroma because of 2, 3-butanediol. Chili oils could be well divided into 3 groups by the partial least squares discriminant analysis (PLS-DA). According to the above results, the 10 kinds of chili oil had their own characteristics in color, capsaicinoids and flavor. Based on quantitative physicochemical indicators and flavor substances, the theoretical basis for the compounding of chili oil could be provided to meet the production demand more scientifically and accurately.
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Capsicum , Cromatografia Gasosa-Espectrometria de Massas , Óleos de Plantas , Paladar , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Capsicum/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos de Plantas/análise , Óleos de Plantas/química , Nariz Eletrônico , Capsaicina/análise , Aromatizantes/análise , Cor , Odorantes/análiseRESUMO
The Dung beetle optimization (DBO) algorithm, devised by Jiankai Xue in 2022, is known for its strong optimization capabilities and fast convergence. However, it does have certain limitations, including insufficiently random population initialization, slow search speed, and inadequate global search capabilities. Drawing inspiration from the mathematical properties of the Sinh and Cosh functions, we proposed a new metaheuristic algorithm, Sinh-Cosh Dung Beetle Optimization (SCDBO). By leveraging the Sinh and Cosh functions to disrupt the initial distribution of DBO and balance the development of rollerball dung beetles, SCDBO enhances the search efficiency and global exploration capabilities of DBO through nonlinear enhancements. These improvements collectively enhance the performance of the dung beetle optimization algorithm, making it more adept at solving complex real-world problems. To evaluate the performance of the SCDBO algorithm, we compared it with seven typical algorithms using the CEC2017 test functions. Additionally, by successfully applying it to three engineering problems, robot arm design, pressure vessel problem, and unmanned aerial vehicle (UAV) path planning, we further demonstrate the superiority of the SCDBO algorithm.
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The dung beetle optimization (DBO) algorithm, a swarm intelligence-based metaheuristic, is renowned for its robust optimization capability and fast convergence speed. However, it also suffers from low population diversity, susceptibility to local optima solutions, and unsatisfactory convergence speed when facing complex optimization problems. In response, this paper proposes the multi-strategy improved dung beetle optimization algorithm (MDBO). The core improvements include using Latin hypercube sampling for better population initialization and the introduction of a novel differential variation strategy, termed "Mean Differential Variation", to enhance the algorithm's ability to evade local optima. Moreover, a strategy combining lens imaging reverse learning and dimension-by-dimension optimization was proposed and applied to the current optimal solution. Through comprehensive performance testing on standard benchmark functions from CEC2017 and CEC2020, MDBO demonstrates superior performance in terms of optimization accuracy, stability, and convergence speed compared with other classical metaheuristic optimization algorithms. Additionally, the efficacy of MDBO in addressing complex real-world engineering problems is validated through three representative engineering application scenarios namely extension/compression spring design problems, reducer design problems, and welded beam design problems.